Abstract 15124: Myocardial Effects of Intermedin and Its Underlying Mechanisms
Intermedin (IMD) a novel peptide related to adrenomedullin (AM) is a potential mediator in the pathogenesis of cardiovascular disease, whose action in the myocardium remains to be elucidated. This study investigated the effects of IMD in myocardial contractility, as well as receptors and pathways involved. The effects of increasing concentrations of IMD (10-8 to 10-6M) were evaluated in isolated rat left papillary muscles in the absence or presence of AM receptors antagonist (AM22-52), CGRP receptor antagonist (CGRP8-37), and of nitric oxide (NO) synthase inhibitor, N(G)-Nitro-L-Arginine (L-NAME), as well as after selective damage of the endocardial endothelium (EE). IMD (10-6) significantly decreased peak twitch active tension (AT) by 14±4% (19±2 vs. 16±1 mN/mm2, P≤0.01) and maximum velocity of tension rise (dT/dtmax) by 11±4% (214±14 vs. 192±12 mN.mm-2.s-1, P≤0.05). Damage of the EE, presence of AM22-52 and CGRP8-37 blunted the inotropic response to IMD. However in the presence of L-NAME IMD induced positive inotropic and lusitropic effects, increasing: AT by 7±3% (19±1 vs 23±1 mN/mm2, P≤0.05), dT/dtmax by 9±3% (288±16 vs. 312±15 mN/mm2.s-1, P≤0.01) and maximum velocity of tension decline (dT/dtmin) by 11±3% (-154±1 vs. -170±2, mN.mm-2.s-1, P≤0.01). This response of IMD in the presence of L-NAME was blunted by CGRP8-37 but not AM22-52. These data provide the first direct evidence of a negative inotropic effect of IMD, mediated by NO, AM and CGRP receptors activation. NO inhibition changed the myocardial response to IMD into positive inotropic and lusitropic effects, mediated by CGRP receptor activation.
- © 2011 by American Heart Association, Inc.